This program requests 4 predoctoral positions for training in immune system development and regulation (ISDR). The program includes 26 trainers with expertise in the development and regulation of the immune system, who are a subset of the Immunology Graduate Group (IGG) at the University of Pennsylvania. This discipline-based training program has a >35-year record of outstanding training. The academic elements of the IGG curriculum form the core experiences for trainees in the ISDR program, and reflect a proven yet evolving mixture of coursework, laboratory rotations, research presentations, and thesis research. These are enriched by a large array of additional activities that foster scientific exchange and discussion, including ongoing activities such as our annual 2.5-day retreat, weekly colloquium, and weekly work-in-progress series, as well as an agreement that affords training with adjunct faculty on the NIH Bethesda campus. The assembled trainers for this grant have highly productive training records in the area of immune system development and regulation, as well as over $75M in annual research support to assure quality and continuity of the training experience. The breadth and strength of the assembled training faculty affords a diverse array of potential trainee mentors. The program has over 100 applicants annually, which are a subset of over 1,000 applicants to biomedical graduate studies at the University of Pennsylvania. The IGG program recruits between 8 to 12 PhD and 2 to 5 MD-PhD trainees per year, yielding a student body of ~60 students, and the ISDR supports a subset of the upper 15% of these. The ISDR focuses specifically on students/faculty whose research is directed towards understanding the development and regulation of the immune system and immune responses. In this regard, the ISDR fosters research training that bears directly on control and manipulation of the immune system in health and disease.